The eye is an extremely sensitive organ. The high sensitivity can be used to accurately determine a wide range of properties of the eye, for example the eye's temporal, spatial and chromatic performance. In turn, these and other properties can yield, directly or indirectly, information pertaining toward the health of the eye.
Due to the importance of the eye and the associated sense of sight, it is not unsurprising that diagnosis and treatment of problems with the eye is the subject of vast amounts of research and development. Of particular interest to many researchers is the retina.
The parts of a human or animal body involved in the processing of light, or ‘the sense of sight’ are, amongst others: a lens, a retina, an optic nerve and a brain.
The retina is the part of the eye upon which light impinges after passing through the lens. The retina is a thin membrane inside the wall of the eye, and comprises a large number of light (and colour) sensitive cells, or ‘photoreceptors’. The retina transforms the light transmitted by the lens into chemical and electrical signals that are sent to the brain via the optic nerve. Maintenance of the health of the retina is crucial to maintaining a healthy eye and thus good sight.
One way of determining the health of the eye is to determine the optical density of one or many of the various constituent components of the retina. One such component is macular pigment. This is a yellow substance located in the central (macular) region of the retina. Macular pigment is believed to be entirely of dietary origin. It is composed of the carotenoids, lutein and xeanthanin.
Research indicates that macular pigment contributes to maintaining the health of the eye in two ways. First, it has anti-oxidant properties, thereby depressing the activity of oxidative substances that are responsible for the degeneration of outer layers of the retina in elderly eyes. Second, it absorbs strongly in the short-wavelength (blue) region of the electromagnetic spectrum, which is known to be damaging to the delicate outer layers of the retina.
The macular region of the eye is prone to degeneration in older people. This condition is particularly debilitating because it affects the ability to drive, read and live a normal life. For example, some people with macular degeneration notice that straight lines in a landscape—such as telegraph poles, the sides of buildings or streets, appear wavy. Other symptoms include blurring of type or a page of print, with dark or empty spaces that may block the centre of the field of vision. Such degeneration is known as age related macular degeneration, or ARM for short. For demographic reasons associated with the aging population, the incidence of age related macular degeneration is on the increase in developed and developing countries, and the potential protective properties of macular pigment has lead to a great deal of interest in its in-vivo measurement.
The benefits of measuring macular pigment are clear. It identifies those patients who are at high risk of developing age related macular degeneration because of low macular pigment. Individuals who have low levels of macular pigment can be advised to modify their lifestyle and diet in a way that is already known to significantly reduce the risk of developing age related macular degeneration. An accurate and reliable measurement of the amount of macular pigment therefore has immense clinical and commercial potential.
In terms of the commercial exploitation, there are now many food supplements containing lutein, which is known to boost the levels of macular pigment in the retina. By measuring the amount of macular pigment from time to time, individuals taking lutein will know how much their macular pigment is increasing due to the ingestion of the lutein. The market for lutein-based products is large and increasing, especially in the United States of America, and manufacturers of the supplements are keen to encourage individuals to be aware of how their eyes are benefiting from the lutein so that they will continue to purchase the lutein-based product. A measurement that yields the amount of macular pigment quickly, accurately and consistently can aid such encouragement.
One aspect of the eye's, and in particular the retina's performance that is of particular interest is the sensitivity to temporal modulation, or ‘flicker’. The human eye is highly sensitive to flicker, and the borderline between the presence and absence of flicker (the flicker threshold) can be easily identified. It is well known in the art that the eye's sensitivity to flicker decreases with age and also with the onset and development of many disease states. In particular, the flicker threshold has been used to determine the amount of macular pigment in the retina, and thus the susceptibility to, onset and progression of age related macular degeneration.
It is well known that sensitivity to temporal modulation of a target is linearly related to the luminance of the target. If two targets are superimposed in space and temporally modulated in anti-phase, the targets appear to flicker only if the luminances of the targets are different. When the relative intensities of the targets are adjusted so that flicker is absent or minimised, then the targets are defined as being of equal luminance as perceived by the eye. This observation is particularly useful when two targets of different wavelength are required to be equalised in luminance, a method called heterochromatic flicker photometry. Such a method is used to determine the amount of macular pigment in the retina.
In a conventional prior art method, the targets are lights of different colours, usually blue and green. The two colours are superimposed and are modulated in anti-phase. The frequency of the modulation is constant, and is usually 15 Hz, although other frequencies such as 10 Hz and 20 Hz have also been used. A subject viewing the superimposed lights perceives them to be flickering. The use of blue light is important as this is preferentially absorbed by the macular pigment. Thus, by comparing the absorption of the blue light in the macular and non-macular (peripheral) parts of the retina, where there is no macular pigment, information relating to the amount of macular pigment can be extracted.
The method requires the subject to view the superimposed lights in such a position that the lights are incident on the macular region of the retina. The subject then adjusts the intensity of the blue flickering light until the flicker disappears. At the point at which flickering is perceived to disappear, the subject has perceived the green and blue light as being of equal intensity.
Although the subject perceives the intensities of the lights to be equal, in reality they are (in general) not. The perceptions of the subject are used to determine properties of the subject's eye, or more specifically their retina.
At the point at which flicker disappears, a ratio of the intensity of blue light and green light is established. For the central (macular) region of the retina, the corresponding luminance of the blue light is known as the central luminance, Lc.
The measurement is repeated for a peripheral part of the retina, where there is no macular pigment. Since there is no macular pigment in the peripheral part of the retina, this measurement acts as a normalisation measurement. The measurement is taken, for example, at an angle of 6° from the macular region. At the point at which flicker disappears, a ratio of the intensity of blue light and green light is established. For the peripheral region of the retina, the corresponding luminance of the blue light is known as the peripheral luminance, LP.
As is known in the art, an indication of the amount of macular pigment in the macular region of the retina can be derived from entering the measured central and peripheral luminances into the following formula:
  MPOD  =            Log      10        ⁡          [                        L          C                          L          P                    ]      where LC and LP are the central and peripheral luminances, and MPOD is the optical density of macular pigment in the macular region.
Although the basic concept of this measurement method is straightforward, its actual implementation is not. This measurement for measuring flicker sensitivity relies on expensive apparatus that needs careful and repeated calibration and a professionally trained operator. Even with such highly stringent conditions, the results obtained are often prone to error and maybe misleading. Similar research studies conducted by different research groups often yield results that are inconsistent at best, with large discrepancies sometimes apparent between the results.
As well as errors inherent in the apparatus used, a wide range of errors is introduced due to each subject's different perceptions and sensitivities to the method used. For example, subjects may have different sensitivities to flicker and colour saturation, both of which will introduce errors into the results obtained from the prior art method. One suggested method of reducing errors in the prior art method is to take the average results of a plurality of measurements. While reducing the errors to a limited extent, such a multi-measurement experiment requires careful control of all physical and psychological factors. In an attempt to control such factors, a professionally trained operator is required. Clearly this is impractical and prevents the method being used on a wide scale, such as in pharmacies and even health centres. In particular, the requirement of a professionally trained operator prevents the method being used by an unskilled user, for example the patient or subject.
Although techniques such as taking the average of a plurality of measurements do result in the reduction of some errors, other errors remain. For example, when exposed to a prolonged period of continuous flicker, the eye's natural response is to adapt to this flicker. Responding to or sensing continuous flicker is energetically inefficient for the eye, and thus the flicker is ‘blurred out’ or, to some extent ‘suppressed’ by the eye. This is known as the Troxler Effect, and is widely known to those skilled in the art. The prior method, which involves exposing a subject to a continuous period of flicker, is consequently prone to errors introduced by the Troxler Effect.